Maintenance of glucose levels is accomplished by finely tuned oscillations of insulin release throughout the day. Individuals with type 2 diabetes (T2D) lose this oscillating pattern of response, and identifying factors that can alter insulin release is important in the prevention of T2D. Changing meal frequency and composition are 2 factors that have been shown to alter the insulin and incretin response. Our preliminary data in healthy individuals demonstrates eating 6-meals in 12-h increases the insulin response throughout the day, while glucose levels remain constant, compared to a 3 meal/day pattern. We observed a similar pattern of response but slightly lower insulin levels with a high-protein meal (6-meals in 12 h). This data suggests meal frequency/composition may alter the insulin pattern of response, which may predispose individuals to T2D. The study proposed herein will elucidate the differences in the glucose, insulin, GLP-1 and ghrelin responses to frequent meals of different dietary composition in obese individuals with metabolic syndrome, and establish if exercise training can attenuate any inappropriate glucose/insulin responses to these feedings. Twelve obese adults with metabolic syndrome will be studied under 3-meal conditions (mixed-meal - 3 feedings, mixed-meal - 6 feedings, high-protein- 6 feedings). Since exercise is known to impact insulin sensitivity, subjects will exercise train for 15 days, and have hormonal responses to the mixed meal- 6 feedings retested. We hypothesize that frequent feeding will result in increasing insulin and GLP-1 and reduced suppression of ghrelin responses in order to maintain glucose levels, regardless of meal composition;and slightly lower responses will be seen with the high protein meal. Further, we hypothesize that exercise training will minimize any increases in insulin that occurs with the frequent meals. This pilot data may offer a potential mechanism for the development of T2D, which will be pursued in future studies by examining potential changes at the muscle level. PUBLIC HEALTH RELEVANCE: Identifying the factors that lead to insulin resistance is critical. Our preliminary data has indicated that eating frequent meals results in higher insulin levels at the end of the day and this may be one factor that leads to insulin resistance. This project will investigate if this same phenomenon occurs in obese subjects with metabolic syndrome. Further this project will determine whether exercise training will minimize any increases in insulin that occurs with the frequent meals.